Retinal ischemia occurs when the oxygen and glucose supply to the retina is interrupted. This condition may occur in retinal vascular diseases such as retinal artery occlusion, or as a result of systemic diseases such as diabetes mellitus. The pathophysiology of retinal injury following ischemia appears to involve excitatory amino acids and disturbances in blood flow. The local concentration of adenosine increases massively during cerebral ischemia, and exogenous adenosine analogues administered to animals before or after ischemia have produced ameliorative effects. An adenosine analogue has been found to attenuate retinal ischemic injury in rabbits, and adenosine appears to be one factor involved in the retinal vascular response to decreased blood oxygen content. The overall hypothesis of this study is that adenosine is a critical factor in the retinal response to conditions where oxygen and./or glucose delivery to the retina is diminished. Based upon this function of adenosine, the use of selective adenosine against, or modulation of endogenous adenosine concentration, may allow manipulation of critical events (excitatory amino acid concentration or blood flow alterations) during or after retinal ischemia. To evaluated the role of adenosine in retinal ischemia, adenosine concentration will be measured in the retina during hypoxic and ischemia. The use of adenosine antagonists under these conditions will allow evaluation of the influence of adenosine on blood flow in the retina. In another series of experiments, we will use selective adenosine agonists either before or after retinal ischemia to examine whether adenosine can provide an attenuation of retinal injury. These studies will provide new information on the role of adenosine in compensatory mechanisms during and after retinal ischemia and potential therapeutic approaches to prevent or ameliorate retinal ischemic injury and visual loss.